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PubMed1992

Protein oxidation associated with aging is reduced by dietary restriction of protein or calories.

The accumulation of unrepaired oxidative damage products may be a major factor in cellular aging. Both oxidative lesions in DNA and oxidatively damaged proteins have been shown to accumulate during aging. The accumulation of oxidized proteins in Fischer 344 rats was compared for animals consuming protein-restricted and calorically restricted diets--both of which have been shown to extend lifespan. Rats were fed diets restricted in either protein (5% or 10% of the diet as compared with the normal 20% casein), or calories (25% or 40% less than normal), or total diet (40% less than normal). In addition, some of the rats fed a diet providing 5% or 20% protein were irradiated twice weekly (125 rads per exposure; 1 rad = 0.01 Gy). The level of oxidative damage to proteins (protein carbonyls) was determined in rats sacrificed at various times. The oxidative damage to proteins increased with aging and with radiation. Either protein or calorie restriction markedly inhibited the accumulation of oxidatively damaged proteins. Protein restriction reduced the accumulation of oxidatively damaged proteins during the oxidative stress of chronic irradiation.

Aging↗

PubMed1985

Nutritional influences on aging of Fischer 344 rats: I. Physical, metabolic, and longevity characteristics.

The aims of this research were (a) to compare food restriction initiated in adult life of male Fischer 344 rats with that limited to early life or involving most of the life span on physical, metabolic, and longevity characteristics and (b) to study a similar level of protein restriction without caloric restriction on these characteristics. Food restriction (60% of the ad libitum intake) initiated at 6 months of age markedly increased life span as did a similar restriction started at 6 weeks of age, but food restriction limited to early life (6 weeks to 6 months of age) and protein restriction caused only a small increase in longevity. Food restriction does not act by reducing the intake of calories or other nutrient per gram of body mass, a finding not in accord with classic views. A progressive decrease in spontaneous locomotive activity with age occurred in ad libitum fed but not restricted rats.

Age Factors↗

PubMed2006

Calorie restriction mimetics: an emerging research field.

When considering all possible aging interventions evaluated to date, it is clear that calorie restriction (CR) remains the most robust. Studies in numerous species have demonstrated that reduction of calories 30-50% below ad libitum levels of a nutritious diet can increase lifespan, reduce the incidence and delay the onset of age-related diseases, improve stress resistance, and decelerate functional decline. A current major focus of this research area is whether this nutritional intervention is relevant to human aging. Evidence emerging from studies in rhesus monkeys suggests that their response to CR parallels that observed in rodents. To assess CR effects in humans, clinical trials have been initiated. However, even if results from these studies could eventually substantiate CR as an effective pro-longevity strategy for humans, the utility of this intervention would be hampered because of the degree and length of restriction required. As an alternative strategy, new research has focused on the development of 'CR mimetics'. The objective of this strategy is to identify compounds that mimic CR effects by targeting metabolic and stress response pathways affected by CR, but without actually restricting caloric intake. For example, drugs that inhibit glycolysis (2-deoxyglucose), enhance insulin action (metformin), or affect stress signaling pathways (resveratrol), are being assessed as CR mimetics (CRM). Promising results have emerged from initial studies regarding physiological responses which resemble those observed in CR (e.g. reduced body temperature and plasma insulin) as well as protection against neurotoxicity (e.g. enhanced dopamine action and up-regulated neurotrophic factors). Ultimately, lifespan analyses in addition to expanded toxicity studies must be accomplished to fully assess the potential of any CRM. Nonetheless, this strategy clearly offers a very promising and expanding research endeavor.

Animals↗

PubMed1994

The use of dietary restrictions in malnourished nursing home patients.

OBJECTIVE: To evaluate the dietary prescriptions of nursing home patients who show evidence of malnutrition. DESIGN: A descriptive chart review. SETTING: Four chronic care facilities in Milwaukee, Wisconsin. PATIENTS: A total of 336 charts were randomly selected from the four facilities. Analysis was done on the 217 charts that included a recorded serum albumin. MAIN OUTCOME MEASURES: Serum albumin, height, most recent weight, weight recorded 6 months previously, major diagnoses, and current diets were recorded. Average weight change per month and body mass index were calculated. RESULTS: In 109 of the 217 patients, the serum albumin was less than 3.5 g/dL. 75.2 percent of hypoalbuminic patients were on some sort of dietary restriction, including caloric restriction in 18% and sodium restriction in 35%. Sixty-six of the 217 patients had an average weight loss of greater than 1 pound per month, and 59% of this group were on dietary restrictions, with 21% on sodium restriction and 20% on limited calories. CONCLUSIONS: Malnutrition is a common problem in the nursing home population. A restricted diet is one possible factor that might contribute to this. While this study does not prove a causal relationship between a restricted diet and malnutrition, it would seem inappropriate that most patients with evidence of malnutrition are on diets that might discourage nutrient intake.

Aged↗

PubMed2001

Intergenerational effect of an adverse intrauterine environment on perturbation of glucose metabolism.

Human epidemiological and animal studies have revealed the late consequences of malnutrition during gestation and early life on the health of the offspring. These studies have highlighted the inverse relationship between birth weight and the incidence of insulin resistance and type 2 diabetes later in life. The aim of this paper is to review the different means of achieving foetal malnutrition and its consequences even for a next generation, in animal models and to identify key area for further research. We address the impact of two models of maternal malnutrition (protein restriction and caloric restriction) as well as the impact of maternal diabetes, the three maternal conditions leading to perturbed foetal nutritional environment. Particular emphasis is given to the endocrine pancreas and the insulin sensitive tissues. More specifically, alterations of the foetal nutritional environment perturb the development of the endocrine pancreas and target the ss cell mass at birth. Some adaptations later in life may take place but stress situations such as pregnancy and ageing precipitate the animals to glucose intolerance and insulin resistance. Even the next generation features alterations in the development of the endocrine pancreas. Some mechanisms by which the foetal ss cell mass is altered are approached in this review and specific attention is paid to the amino acid profile. The preventive role of taurine is discussed.

Animals↗

PubMed2006

Short-term changes in insulin resistance following weight loss surgery for morbid obesity: laparoscopic adjustable gastric banding versus laparoscopic Roux-en-Y gastric bypass.

BACKGROUND: Laparoscopic adjustable gastric banding (LAGB) and laparoscopic Roux-en-Y gastric bypass (LRYGBP) both effectively treat the insulin resistance associated with type 2 diabetes mellitus (T2DM). Restriction of caloric consumption, alterations in the entero-insular axis or weight loss may contribute to lowering insulin resistance after these procedures. The relative importance of these mechanisms, however, following LAGB and LRYGBP remain unclear. The aim of this study was to compare directly the short-term changes in insulin resistance following LAGB and LRYGBP in similar populations of patients. METHODS: Patient preference determined operation type. The Homeostasis Model Assessment for Insulin Resistance (HOMA IR) was used to measure insulin resistance. Preoperative values were compared to postoperative levels obtained within 90 days of surgery. Significant differences between groups were tested by ANOVA. RESULTS: There were no significant preoperative differences between groups. The 56 LAGB patients had a mean age of 42.5 years (25.7-63), BMI of 45.5 kg/m(2) (35-66) and preoperative HOMA IR of 4.1 (1.4-39.2). 75% of LAGB patients were female and 43% had T2DM. The 61 LRYGBP patients had a median age of 39.9 years (22.1-64.3), BMI of 45.0 kg/m(2) (36-62), and preoperative HOMA IR of 5.0 (0.6-56.5). 79% of LRYGBP patients were women and 44.3% had T2DM. Median follow-up for LAGB patients was 45 days (18-90) and for LRYGBP patients 46 days (8-88 days). LAGB patients had a median of 14.8% excess weight loss (6.9%-37.0%) and LRYGB patients 24.2% (9.8%-51.4%). Postoperative HOMA IR was significantly less after LRYGBP, 2.2 (0.7-12.2), than LAGB, 2.6 (0.8-29.6), although change in HOMA IR was not significantly different. Change in HOMA IR for both groups did not vary with length of follow-up or weight loss but correlated best with preoperative HOMA IR (LAGB r=0.8264; LRYGBP r=0.9711). CONCLUSIONS: Both LAGB and LRYGBP significantly improved insulin resistance during the first 3 months following surgery. Both operations generated similar changes in HOMA IR, although postoperative HOMA IR levels were significantly lower after LRYGBP. These findings suggest that caloric restriction plays a significant role in improving insulin resistance after both LAGB and LRYGBP.

Adult↗

PubMed1990

Management strategies for weight control. Eating, exercise and behaviour.

Obesity is a major health and social problem worldwide for which no single satisfactory treatment exists. Because of the prevalence of the disease, numerous therapeutic strategies have been attempted--often unsuccessfully. Weight loss programmes based on dietary restriction of caloric intake and nutritional education, exercise, surgical (gastroplasty, gastric bypass) and procedural (gastric balloon, waist cord, jaw wiring, liposuction) intervention and pharmacotherapy (appetite suppressants, thermogenic agents, bulking agents) used alone or in combination, have produced weight loss in the short to medium term; however, weight is generally regained on discontinuation of treatment. Behaviour modification programmes appear to offer the highest success rate in the long term. Weight loss is not rapid, although losses of 10 to 15 kg have been achieved after 6 months, and this may be increased when behaviour modification therapy is combined with more aggressive treatments such as severe caloric restriction or jaw wiring. Behaviour modification is particularly beneficial in special patient groups such as the obese elderly, children or adolescents, and disabled patients. Thus, although it appears that each of the treatments developed for the management of obese patients has its place, the cornerstone of therapy for most patients remains a programme of dietary restriction, combined with exercise and behaviour modification.

Behavior Therapy↗

PubMed1981

Long-term effects of early iron deficiency on consummatory behavior in the rat.

Two experiments were designed to investigate the effects of early iron deficiency on consummatory behavior in the adult rat. In experiment 1, animals were placed in a novel chamber, either with or without water available. Although there were no effects of iron deficiency per se, the data suggested that decreased caloric intake experienced early in life may have different long-term consequences for males and females. While ad lib control males, and females in all diet conditions, exhibited less elevation of plasma corticosterone when water was available in the novel chamber, calorically restricted males appeared unable to use the cues or reinforcement provided by consummatory behavior to reduce arousal. In Experiment 2, a conditioned taste aversion situation involving conflict, we were able to separate effects due to early iron deficiency from those due to early caloric restriction. When reexposed to milk, calorically restricted (weight control) males exhibited an attenuated plasma corticoid response, compared to that of ad lib control males, while weight control females resembled ad lib control females in their response. Thus, as in Experiment 1, early caloric restriction affected males more than females. Early iron deficiency, however, markedly altered pituitary-adrenal responsiveness in both males and females. Not only was the response to reexposure completely reversed in rehabilitated males and females, but also, the corticoid response to deprivation was increased in rehabilitated males and decreased in rehabilitated females. Taken together with previous data, these results suggest that early iron deficiency alters both behavioral and physiological arousal or responsiveness, and may do so differentially in males than females.

Animals↗

PubMed1989

Exercise and deficient carbohydrate storage and intake as causes of hypoglycemia.

Exercise is associated with a marked increase in glucose uptake by muscle, which is initially supported by breakdown of hepatic glycogen and subsequently by increased gluconeogenesis. If hepatic glucose production is inadequate, hypoglycemia results. During exercise there is decreased plasma insulin and increased catecholamines, glucagon, cortisol, and growth hormone, which contribute to but are not essential for the increased hepatic output of glucose. Although insulin concentrations fall, insulin sensitivity is increased. However, the augmented glucose uptake by muscle is due to other factors. The symptoms of exhaustion during exercise are not due to hypoglycemia, and prevention of hypoglycemia may not prolong the time of exercise to exhaustion. During severe caloric restriction, hepatic glucose production decreases and free fatty acids and ketone bodies become important sources of calories. Although under these circumstances hepatic gluconeogenesis is usually sufficient to prevent hypoglycemia, with very severe caloric restriction hypoglycemia can result. With starvation, insulin concentrations fall while growth hormone and glucagon increase. Frequently the usual symptoms of hypoglycemia are absent in individuals with hypoglycemia from severe caloric restriction. Hypoglycemia from severe caloric restriction has not been totally restricted to underdeveloped areas of the world. In such patients no endocrine abnormalities have been found, and hypoglycemia has persisted despite administration of large amounts of carbohydrate. Pregnancy and lactation could predispose to hypoglycemia in the face of inadequate caloric intake.

Adult↗

PubMedDate not supplied

Blood pressure and hormone changes associated with weight reduction in the obese.

This study examines factors modulating blood pressure reduction in obese patients undergoing weight reduction on a low calorie protein diet. Plasma norepinephrine (NE) was correlated (r = 0.65, p less than 0.01) with blood pressure in 20 obese patients prior to weight loss. Reductions in blood pressure levels following upright posture and isometric handgrip exercise were related to reduction in NE levels after these maneuvers. While plasma epinephrine levels declined in parallel with NE levels, plasma dopamine actually increased (p less than 0.05) during the first 2 weeks of caloric restriction. Prior to weight loss the obese patients demonstrated a significant rise in prolactin levels following posture and exercise, but following caloric restriction this was not observed. Levels of plasma renin activity (PRA) and aldosterone obtained after posture and exercise maneuvers were reduced after 8 weeks of caloric restriction, and reductions in PRA were related to reductions in NE (r = 0.56, p less than 0.01). Reductions in blood pressure in association with caloric restriction in these obese patients seems to result, in part, from reduced sympathetic nervous system activity as well as secondary effects of reduced adrenergic activity on renal sodium excretion and the renin-angiotensin-aldosterone axis.

Adult↗

PubMed1998

Neuropeptide Y (NPY) levels in alcoholic and food restricted male rats: implications for site selective function.

Neuropeptide Y (NPY) has been implicated in the control of ingestive, cardiovascular, and reproductive function. Blood pressure and sexual function were examined in Long-Evans rats receiving 6% ethanol-containing or calorically matched liquid diets, or rat chow ad lib. After 12 weeks of exposure, rats were sacrificed and plasma hormone levels and NPY content of microdissected brain regions were determined. Neither long-term alcohol ingestion nor caloric restriction were associated with major decrements in copulatory behavior. Long-term alcohol ingestion was associated with decrements in erectile function ex copula. Long-term alcohol ingestion was also associated with: (i) a moderate degree of hypertension; (ii) a failure to gain weight; (iii) decrements in circulating levels of LH, testosterone, and ACTH (but not progesterone); and (iv) increased corticosterone levels. Long-term alcohol ingesting and calorically-restricted rats exhibited alterations in daily feeding patterns. These physiological changes in response to long-term alcohol ingestion or caloric restriction were associated with neural site-selective differences in NPY content. Elevated NPY in the paraventricular nucleus was associated with voluntary (as in alcohol ingestion) or involuntary (as in caloric restriction) reductions in food intake. Differences in NPY in the suprachiasmatic and ventromedial nuclei were associated with the differences in feeding patterns. The decrements in hormone levels were associated with higher levels of NPY in the median eminence and in the arcuate nucleus.

Adrenocorticotropic Hormone↗

PubMed1986

Ventilatory and treadmill endurance during acute semistarvation.

Little is known about respiratory muscle function in acute undernutrition, although an inadequate caloric intake is common in numerous disease states. Twelve young-adult, healthy female volunteers performed two familiarization experiments and were then studied after 7 days of consuming 40% of normal daily caloric intake as well as after 1 wk of normal caloric intake. In each experiment subjects performed tests of resting pulmonary function, inspiratory muscle strength, and ventilatory endurance, the last of which involved two 60-s and two 6-min isocapnic maximum voluntary ventilation maneuvers. Subjects then walked to exhaustion in 8-20 min on a treadmill. The caloric restriction did not affect performance of any breathing test but did lower endurance time in severe treadmill exercise (P less than 0.05). Basal metabolic rate was lowered, resting blood levels of free fatty acids and beta-hydroxybutyrate elevated, and glucose lowered following the caloric restriction (P less than 0.05). Blood lactate levels were lower during and after exercise following caloric restriction (P less than 0.05). We conclude that ventilatory muscle strength and endurance are fully preserved in caloric restriction severe enough to cause mild ketoacidosis and hypoglycemia, lowered basal metabolic rate, and decreased endurance in severe treadmill exercise.

Acute Disease↗

PubMed1984

Effect of an intraluminal food-bulk on low calorie induced hyperbilirubinaemia.

To test the hypothesis that the presence of food in the intestine plays a role in the control of serum bilirubin levels, the effect of a 1674 kJ (400 kcal) diet, including non-absorbable material able to produce an intestinal bulk, was compared with the effect of caloric restriction alone. In normal individuals (n = 10) the rise of plasma bilirubin was comparable after the two trials. In patients with Gilbert's syndrome (n = 18), bilirubin concentration rose to a much greater extent during the caloric restriction as compared with controls, and to a lesser extent (P less than 0.001) after the bulky diet, as compared with caloric restriction alone in the same patient. It is proposed that a factor originating from the intestine, perhaps a hormone, the release of which is dependent on the presence of food-bulk, plays a role in the control of hyperbilirubinaemia associated with caloric restriction.

Adult↗

PubMed1999

The leptin-fat ratio is constant, and leptin may be part of two feedback mechanisms for maintaining the body fat set point in non-obese male Fischer 344 rats.

While plasma leptin and adiposity have been found to be strongly related, the specific nature of this relationship has yet to be clarified. Hence, plasma leptin and three indicators of adiposity were measured in adult male Fischer 344 rats on three different long-term diets: continuous ad libitum feeding; ad libitum feeding until early adulthood, then continuous 60% caloric restriction; and ad libitum feeding until early adulthood, then 60% caloric restriction until 16 months, then ad libitum feeding for 5 months. Body fat was found to be a good linear correlate of plasma leptin, with a zero Y-intercept, and a constant plasma leptin-body fat ratio. The number of adipocytes per rat and % body fat were strong quadratic correlates of plasma leptin. This study is the first to find a zero Y-intercept and constant plasma leptin-body fat ratio, probably because it is the first to simultaneously measure both plasma leptin and body fat accurately, and to account for confounders such as gender, genetic background, age, physical activity, and possibly obesity. The study also explored the effect of switching calorically-restricted rats to ad libitum feeding. This led to a rapid rise, and then synchronized up-down cycles in average daily food intake and body weight, with a steady upward trend toward a new stable body-weight set point. It is hypothesized that this pattern resulted from two simultaneous feedback mechanisms, possibly involving leptin. In conclusion, this study suggests that, under controlled conditions, the plasma leptin-body fat ratio is a constant for a particular mammalian strain, independent of dietary history.

Adipose Tissue↗

PubMed2003

Meal size and frequency affect neuronal plasticity and vulnerability to disease: cellular and molecular mechanisms.

Although all cells in the body require energy to survive and function properly, excessive calorie intake over long time periods can compromise cell function and promote disorders such as cardiovascular disease, type-2 diabetes and cancers. Accordingly, dietary restriction (DR; either caloric restriction or intermittent fasting, with maintained vitamin and mineral intake) can extend lifespan and can increase disease resistance. Recent studies have shown that DR can have profound effects on brain function and vulnerability to injury and disease. DR can protect neurons against degeneration in animal models of Alzheimer's, Parkinson's and Huntington's diseases and stroke. Moreover, DR can stimulate the production of new neurons from stem cells (neurogenesis) and can enhance synaptic plasticity, which may increase the ability of the brain to resist aging and restore function following injury. Interestingly, increasing the time interval between meals can have beneficial effects on the brain and overall health of mice that are independent of cumulative calorie intake. The beneficial effects of DR, particularly those of intermittent fasting, appear to be the result of a cellular stress response that stimulates the production of proteins that enhance neuronal plasticity and resistance to oxidative and metabolic insults; they include neurotrophic factors such as brain-derived neurotrophic factor (BDNF), protein chaperones such as heat-shock proteins, and mitochondrial uncoupling proteins. Some beneficial effects of DR can be achieved by administering hormones that suppress appetite (leptin and ciliary neurotrophic factor) or by supplementing the diet with 2-deoxy-d-glucose, which may act as a calorie restriction mimetic. The profound influences of the quantity and timing of food intake on neuronal function and vulnerability to disease have revealed novel molecular and cellular mechanisms whereby diet affects the nervous system, and are leading to novel preventative and therapeutic approaches for neurodegenerative disorders.

Animals↗

PubMed2002

A low-calorie diet improves endothelium-dependent vasodilation in obese patients with essential hypertension.

BACKGROUND: Both obesity and hypertension are associated with endothelial dysfunction. The purpose of this study was to investigate the effects of a low-calorie diet on endothelial function in obese patients with essential hypertension. METHODS: We measured forearm blood flow (FBF) during intra-arterial infusion of acetylcholine (ACh; 7.5, 15, 30 microg/min), an index of endothelium-dependent vasodilation, and isosorbide dinitrate (ISDN; 0.75, 1.5, 3.0 microg/min), an index of endothelium-independent vasodilation, in obese patients with essential hypertension before and after 2 weeks on a low-calorie diet (800 kcal/d). The study included 11 obese hypertensive Japanese patients (mean body mass index, 30.8 +/- 3.6 kg/m2). Fifteen healthy Japanese normotensive individuals were recruited as a control group. RESULTS: In obese patients with hypertension, the response of FBF to ACh was attenuated compared to healthy individuals (P < .001). Caloric restriction reduced body weight from 77.5 +/- 15.0 to 73.2 +/- 13.5 kg (P < .01), the mean blood pressure from 118.4 +/- 8.7 to 105.7 +/- 8.5 mm Hg (P < .01), fasting plasma insulin from 85.8 +/- 22.8 to 64.8 +/- 27.0 pmol/L (P < .05), serum total cholesterol from 5.30 +/- 0.76 to 4.67 +/- 0.58 mmol/L (P < .05), and low density lipoprotein cholesterol from 3.80 +/- 0.48 to 3.29 +/- 0.44 mmol/L (P < .05). Basal FBF was similar before and after weight reduction. Caloric restriction enhanced the response of FBF to ACh (P < .05), but did not alter the response to ISDN. The intra-arterial infusion of NG-monomethyl-L-arginine (8 micromol/min), a nitric oxide synthase inhibitor, decreased the enhanced ACh-induced blood flow response induced by caloric restriction. CONCLUSIONS: The present findings suggest that the caloric restriction improves endothelial-dependent vasodilation through an increased release of nitric oxide in obese hypertensive patients.

Acetylcholine↗

PubMed1991

Hypocaloric diets and ketogenesis in the management of obese gestational diabetic women.

The extent to which given levels of caloric restriction will improve glycemic status but increase plasma ketone bodies in gestational diabetic women has received little attention. After reviewing the underlying physiology, we present data on two feeding studies investigating the question. In the first, a weight-maintaining approximately 2400-kcal/day diet was fed on a metabolic ward to 12 gestational diabetic women for 1 week. In the second week, subjects were randomized to a continuation of the 2400-kcal/day diet or to a 1200-kcal/day diet. Twenty-four-hour mean glucose levels remained unchanged in the control group but declined in the calorie-restricted group (6.7 mM or 121 mg/dl in week 1 vs 5.4 mM or 97.3 mg/dl in week 2) (p less than 0.01). Nine-hour overnight fasting plasma insulin also declined but oral glucose tolerance did not improve with caloric restriction. Fasting plasma beta-hydroxybutyrate rose in the calorie-restricted group, along with an increase in ketonuria, but not in the control group. A second study compared the impact of a 33% calorie-restricted diet or insulin to a full-calorie diet in a similar 2-week experimental design and measured hepatic glucose output and insulin sensitivity with dideuterated glucose before and during an insulin clamp. Diet in three subjects improved fasting and 24-hr mean glucose by 22 and 10%, respectively, whereas prophylactic insulin in three subjects produced 0 and 4% reductions, respectively. On average, ketonuria after a 9-hr fast declined to an equivalent degree with both treatments. Hepatic glucose output and insulin sensitivity were not statistically significantly altered by gestational diabetes or the therapeutic interventions compared to nondiabetic normal weight or obese pregnant controls. In conclusion, 50% caloric restriction improves glycemic status in obese women with gestational diabetes but is associated with an increase in ketonuria, which is of uncertain significance. An intermediate 33% level of caloric restriction (to 1600-1800 kcal daily) may be more appropriate in dietary management of obese woman with gestational diabetes mellitus and more effective than prophylactic insulin. Further studies are required to confirm these findings.

Animals↗

PubMed2001

Food deprivation limits insulin secretory capacity in postpubertal rats.

ABSTRACT Because prenatal and perinatal undernutrition are associated with type 2 diabetes later in life, we posed the question whether nutrient deprivation during puberty would also result in a decreased ability to secrete insulin. Chronically catheterized, unstressed Sprague Dawley rats, fed ad libitum, were studied before puberty (Pre, n = 14) and after puberty (Post, n = 8). Moderately caloric-restricted rats (fed 70% of the control diet, n = 9), were studied after puberty. Insulin secretion was assessed using a hyperglycemic clamp at a glucose concentration of 300 mg/dL, or with a primed continuous infusion of intralipid (plasma FFA levels approximately 1.5 mM) at a plasma glucose concentration of 200 mg/dL. Stimulated insulin levels increased in Post rats by 3- to 4-fold compared with Pre rats (from 4.6 +/- 0.4 ng/mL Pre to 12.8 +/- 0.7 ng/mL Post, and from 4.5 +/- 0.4 ng/mL Pre to 15.8 +/- 0.7 ng/mL Post, respectively, p < 0.001, at a glucose concentration of 300 mg/dL, and 200 mg/dL with intralipid). Caloric restriction prevented any rise in insulin secretion (3.8 +/- 0.5 and 4.6 +/- 0.5 ng/mL in the caloric-restricted rats at glucose concentrations of 300 mg/dL and 200 mg/dL with intralipid, respectively). A semiquantitative reverse-transcriptase PCR procedure was used to assess basal and stimulated insulin mRNA levels. Caloric restriction did not compensate by enhancing insulin mRNA levels in response to glucose stimulation. Moderate food deprivation during puberty reduced the capacity of the pancreas to secrete insulin in response to different nutrient stimuli. We hypothesize that puberty has an important role in beta-cell maturation and any major nutrient modification may have deleterious consequences later in life.

Animals↗